Sunday, February 3, 2013

Nature vs. Nurture as the Cause of Mental Illness

Kristin Sheppard

Over the
last few years, I’ve had several friends begin their battles with mental
illness. For some it was a short lived depressive episode, for others it has
been much more serious with chronic depression and even schizophrenia. All
this begs the question: are these battles the result of nature or nurture?

The public
as a whole seems to be very torn on whether mental illness is the result of a
person’s genetics or if it is due to their environment. Back in the 1960’s and 1970’s it was commonly
believed that mental illness was caused by bad parenting and “the refrigerator
mother.” By the late 1990’s it was still widely believed that a current
stressful environment and neglectful upbringing was the major cause; but it
also became more popular to cite a “chemical imbalance” as the cause of mental
illness (though the public never seemed to know what these “chemicals” were). Even now, when searching through literature,
it is equally as common to find journal articles that claim genetic factors are
the major cause as it is to find articles claiming societal or environmental
factors are the major cause. So if both
the “experts” and the public at large are so confused about the cause of mental
illnesses, how are we supposed to know how to prevent it? Are we all just
ticking time bombs?

It turns
out, the answer to the question of the cause of mental illness being nature or
nurture may be as simple as: both. This year an article was published in Science about epigenetic causes of
adult-onset psychiatric disorders. Now, most of the time when you tell someone
that something is caused by epigenetics, they will respond with
“eh-pee-jah-what?” So when you go and tell all your friends about this article,
you can just tell them that epigenetic changes are changes to how your cells
read your DNA without changing the sequence of your DNA base-pairs. These
researchers focused specifically on how environmental stressors in childhood
and adolescence cause an epigenetic change, and it is this change that causes
the adult onset mental illnesses that we have been talking about.

In this
study, mouse models were used to emulate different possible causes of mental
illness. These groups of mice received one of four different treatments: only
genetic risk factors, only environmental stressors, no genetic risk factors or
environmental stressors, or both genetic risk factors and environmental
stressors. To create the genetic risk factor the researchers created a mutation
in the gene for a protein called DISC1 (which stands for “Disrupted In
Schizophrenia 1”) to alter the normal protein that is produced naturally by
cells. In humans changes to the DISC1 gene is thought to cause a predisposition
to disorders such as schizophrenia, clinical depression, and bipolar disorder. The
environmental stressor was created by placing young mice in isolated cages for
3 weeks during brain development; since mice are social animals, this treatment
is thought to mimic the stress of separation from parents and family in human
children and adolescents.

The
researchers found that only mice in the group that had both the genetic risk
factor and the environmental stressor displayed behavioral symptoms that would
indicate mental illness in humans. These behavioral symptoms included
significant deficiencies in locomotor activity and swim tests. These symptoms
were present in both males and females within this treatment group, but no
observable physical changes (such as gain or loss of body weight) were
initially found to explain them.

When the
brains for each group were studied, there was no significant difference in the
number of neurons or glial cells present indicating that these symptoms were
not caused by an anatomical difference in the brain.

However, it
was found that in mice that had the genetic factor and the environmental
stressor there was a significant decrease in the amount of dopamine and
tyrosine hydroxylase (a precursor for dopamine) present in the frontal cortex
of the brain compared to all of the other treatment groups. Dopamine is one of
the chemicals involved in communication between neurons, and is known to play a
role in reward-driven learning. Highly addictive drugs such as methamphetamine
cause the release of excessive amounts of dopamine, where diseases like
Parkinson’s that are characterized by tremors and decreased motor function are
caused by the degeneration of dopamine releasing neurons. So if a combination
of genetic factors and environmental factors can cause a decrease in this
chemical, it is unsurprising that these mice’s behavior shows a decrease in
motor function.

They were
also able to show that the decrease in dopamine was related to the significant
increase of corticosterone in these mice. The human equivalent of
corticosterone is called cortisol, and has been shown to be significantly
increased with stress. Humans with chronically high levels of stress will also
have chronically high levels of cortisol.
It has also been reported that cortisol can influence a type of
epigenetic change called DNA methylation.

Finally, it
was found that mice that had received both the genetic factor and the
environmental stressor had a significant increase in the amount of DNA
methylation on the gene for tyrosine hydroxylase (i.e. the gene that causes the
production of dopamine). This increase in DNA methylation persisted even after the
mice had been back in group housing for 12 weeks (a relatively large portion of
a mouse’s life!).

So let’s
recap. We know that high levels of stress cause higher levels of cortisol.
Cortisol can cause epigenetic changes known as DNA methylation to the gene that
produces the precursor for dopamine.
These epigenetic changes cause less dopamine to be produced. Less
dopamine causes less motor function. Less motor function is an indicator of
mental illness in mice.

But that
leaves the question: how does this relate to us? If the decreased motor
function in the mice in fact translates to mental illness in humans, then it
means that genetic predisposition or environmental stressors during childhood
alone will not cause adult-onset mental illness. Both must be present for one
of these disorders to occur.

2 comments:

Kristin: The contemporary psychological/psychiatric community deals with thisdebate neatly by labeling an individual as being either diagnosed or undiagnosed. You show me one individual out there that could be accurately labeled as clinically normal. That individual just doesn't exist.

I really liked how readable and interesting your take was on a complex, multifaceted issue. In humans, have there be any studies on the function of the DISC1 protein or has it just been shown to correlate with certain mental disorders? Great blog!